Staphylococcus aureus is an opportunistic bacterial pathogen responsible for a diverse spectrum of human and animal diseases. Approximately 75% of S. aureus strains from humans are encapsulated. The prevalence of encapsulation among bovine isolates is variable, depending upon the geographic source of the isolate. An understanding of the role of the staphylococcal capsule in the pathogenesis of S. aureus infections is important. This FIRCA application is a supplement to Dr. Jean Lee's RO1 AI29040 grant to study the genetics of capsule production by S. aureus. The proposed research will be performed primarily in Argentina at the University of Buenos Aires by Dr. Daniel Sordelli and his colleagues. The objectives of the FIRCA project complement those of Dr. Lee's grant and are specifically related to specific aim #3. Under that aim, S. aureus isolates have been identified that lack the capsule genetic locus and carry an IS257-1ike element in its place. The proposed study will: 1) Investigate the loss of the cap5/8 gene cluster in NT S. aureus and the potential role of the IS257 element in such a mechanism. Whether copies of IS257 are associated with cap5/8 locus in S. aureus and whether loss of the cap5(8) genes can occur in vivo will be determined. The in vivo infections will include a systemic model of bacteremia leading to renal abscess formation and the mouse mastitis model of localized infection. 2) Determine whether CP5 or CP8 production enhances staphylococcal virulence in a mouse model of experimental mastitis. 3) Evaluate the effect of CP expression on S. aureus clumping factor A-mediated adherence to fibrinogen. The proposed research will permit further exploration of issues not covered by our currently funded projects, and the information that will emerge from it will expand our knowledge of S. aureus capsular polysaccharide biology.